The safety and adverse event profile of favipiravir in the treatment of COVID-19 patients, Turkey.

INTRODUCTION: Favipiravir (FVP) is an antiviral and used to treat COVID-19. We aimed to document the safety and adverse events associated with FVP on the outcome of COVID-19 treatment. METHODOLOGY: The study included 225 adult patients with moderate COVID-19 infection (World Health Organization scale-5). The adverse events (AEs) were evaluated using a grading scale supported by the Food and Drug Administration. Safety was assessed by the frequency of serious AEs. RESULTS: The AEs associated with FVP treatment were hepatotoxicity (87/225, 38.7%), weakness (32/225, 14.2%), nephrotoxicity (26/225, 11.6%), nausea (18/225, 8.0%), diarrhea (8/225, 3.6%), vomiting (5/225, 2.2%), and insomnia (4/225, 1.8%); rash was not detected. Hepatotoxicity was observed more frequently in patients who also developed nephrotoxicity (57.7% vs 36.2%, p = 0.03). The deceased patients were significantly older and had higher prevalence of hypertension, congestive heart failure (CHF), coronary artery disease, cancer, nephrotoxicity. and angiotensin- converting enzyme inhibitors/angiotensin receptor blocker use. While male gender (OR: 5.38 CI: 1.64-17.67) and CHF (OR: 6.8 CI: 1.92-24.74) were significantly associated with nephrotoxicity, age (OR: 1.06 CI: 1.02-1.10), cancer (OR: 3.9 CI: 1.10-14.22) and nephrotoxicity (OR: 5.5 CI: 1.74-17.74) were associated with mortality. CONCLUSIONS: Serious AEs were detected at very low levels that would not require discontinuation of treatment or any AE-related death. Since SARS-CoV-2 itself and drug interactions may differ, FVP-related AEs might vary in COVID-19 patients. Our study shows that FVP can be used safely with a low AE profile. More extensive evidence is required to evaluate the long-term AEs of FVP.

Determinants of Severe Nocturnal Hypoxemia in Adults with Chronic Thromboembolic Pulmonary Hypertension and Sleep-Related Breathing Disorders.

OBJECTIVES: We aimed to investigate the occurrence of sleep-related breathing disorders (SRBDs) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and addressed the effect of pulmonary hemodynamics and SRBD indices on the severity of nocturnal hypoxemia (NH). METHODS: An overnight polysomnography (PSG) was conducted in patients with CTEPH, who were eligible for pulmonary endarterectomy. Pulmonary hemodynamics (mean pulmonary arterial pressure (mPAP), pulmonary arterial wedge pressure (PAWP), pulmonary vascular resistance (PVR) measured with right heart catheterization (RHC)), PSG variables (apnea-hypopnea index (AHI)), lung function and carbon monoxide diffusion capacity (DLCO) values, as well as demographics and comorbidities were entered into a logistic regression model to address the determinants of severe NH (nocturnal oxyhemoglobin saturation (SpO2) < 90% under >20% of total sleep time (TST)). SRBDs were defined as obstructive sleep apnea (OSA; as an AHI ≥ 15 events/h), central sleep apnea with Cheyne-Stokes respiration (CSA-CSR; CSR pattern ≥ 50% of TST), obesity hypoventilation syndrome (OHS), and isolated sleep-related hypoxemia (ISRH; SpO2 < 88% under >5 min without OSA, CSA, or OHS). RESULTS: In all, 50 consecutive patients (34 men and 16 women; mean age 54.0 (SD 15.1) years) were included. The average mPAP was 43.8 (SD 16.8) mmHg. SRBD was observed in 40 (80%) patients, of whom 27 had OSA, 2 CSA-CSR, and 11 ISRH. None had OHS. Severe NH was observed in 31 (62%) patients. Among the variables tested, age (odds ratio (OR) 1.08, 95% confidence interval [CI] 1.01-1.15; p = 0.031), mPAP (OR 1.11 [95% CI 1.02-1.12; p = 0.012]), and AHI (OR 1.17 [95% CI 1.02-1.35; p = 0.031]) were independent determinants of severe NH. CONCLUSIONS: Severe NH is highly prevalent in patients with CTEPH. Early screening for SRBDs and intervention with nocturnal supplemental oxygen and/or positive airway pressure as well as pulmonary endarterectomy may reduce adverse outcomes in patients with CTEPH.

Obstructive Sleep Apnea and Cardiovascular Disease: Where Do We Stand?

Obstructive sleep apnea is common in adults with cardiovascular disease. Accumulating evidence suggests an association between obstructive sleep apnea and cardiovascular disease independent of the traditionally recognized cardiovascular disease risk factors. Observational studies indicate that obstructive sleep apnea is a risk factor for development of cardiovascular disease and that alleviation of obstructive events with positive airway pressure may improve cardiovascular disease outcomes. However, recent randomized controlled trials have not supported the beneficial effect of positive airway pressure in cardiac populations with concomitant obstructive sleep apnea. Some evidence suggests that the relationship between obstructive sleep apnea and traditionally recognized cardiovascular disease risk factors is bidirectional, suggesting that patients with cardiovascular disease may also develop obstructive sleep apnea and that efficient treatment of cardiovascular disease may improve obstructive sleep apnea. Recent data also indicate that the apnea-hypopnea index, which is commonly used as a diagnostic measure of obstructive sleep apnea severity, has limited value as a prognostic measure for cardiovascular disease outcomes. Novel markers of obstructive sleep apnea-associated hypoxic burden and cardiac autonomic response seem to be strong predictors of adverse cardiovascular disease outcomes and response to treatment of obstructive sleep apnea. This narrative review and position paper from the Turkish Collaboration of Sleep Apnea Cardiovascular Trialists aims to update the current evidence about the relationship between obstructive sleep apnea and cardiovascular disease and, consequently, raise awareness for health professionals who deal with cardiovascular and respiratory diseases to improve the ability to direct resources at patients most likely to benefit from treatment of obstructive sleep apnea and optimize treatment of the coexisting cardiovascular diseases. Moreover, the Turkish Collaboration of Sleep Apnea Cardiovascular Trialists aims to contribute to strengthening the efforts of the International Collaboration of Sleep Apnea Cardiovascular Trialists in this context.

Pre-existing Immunocompromised Status as a Preventer of Mortality in COVID-19 Patients: Friend or Foe?

Objective COVID-19 has been negatively impacted by a number of comorbidities. Aside from that, some conditions or treatments that cause immunosuppression can alter the course of the disease, leading to worse outcomes. The primary goal of this study is to compare the clinical presentation, laboratory analysis, radiological findings, and outcomes of patients with COVID-19 with and without immunosuppression. Materials and methods The study includes patients with pre-existing immunosuppression and COVID-19 infection who were admitted and received inpatient treatment at Marmara University Hospital, Istanbul, Pulmonary Medicine ward between April 2020 and June 2020. Data on demographics, epidemiology, clinical course, laboratory analysis, radiological findings, length of hospital stay, morbidity, and mortality were collected from all patients. Results The study group consisted of 23 patients who had pre-existing immunosuppression, and the control group consisted of 207 immunocompetent patients, making a total of 230 patients. Significant differences in lymphocyte count, ROX (respiratory-rate oxygenation) index on Day 0, and fibrinogen levels were discovered between the two groups. SARI (severe acute respiratory infection) was more common in the control group than in the study group (p<0.022), but there was no difference in mortality. Conclusion The mean number and percentage of lymphocytes were lower in immunocompromised COVID-19 patients at the time of diagnosis. Higher ROX index values and a lower risk of developing SARI could explain the hypothesis that these patients may be benefiting from a pre-existing corticosteroid regimen. Additional research with larger numbers of patients may be beneficial in drawing a more definitive conclusion.

Factors Associated with 28-day Critical Illness Development During the First Wave of COVID-19.

Objective: This study aimed to define the predictors of critical illness development within 28 days postadmission during the first wave of the COVID-19 pandemic. Materials and Methods: We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020. Results: The most common presenting symptoms were cough, dyspnea, and fatigue. Critical illness developed in 45 (9.4%; 95% CI=7.0%-12.4%) patients. In the multivariable analysis, age (hazard ratio (HR)=1.05, p<0.001), number of comorbidities (HR=1.33, p=0.02), procalcitonin ≥0.25 µg/L (HR=2.12, p=0.03) and lactate dehydrogenase (LDH) ≥350 U/L (HR=2.04, p=0.03) were independently associated with critical illness development. The World Health Organization (WHO) ordinal scale for clinical improvement on admission was the strongest predictor of critical illness (HR=4.15, p<0.001). The patients hospitalized at the end of the study period had a much better prognosis compared to the patients hospitalized at the beginning (HR=0.14; p=0.02). The C-index of the model was 0.92. Conclusion: Age, comorbidity number, the WHO scale, LDH, and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seemed to be decreasing as the first wave of the pandemic advanced. Graphic Abstract: Graphic Abstract.

Frequency of Obstructive Sleep Apnea in Patients With Cystic Fibrosis and Non-cystic Fibrosis Bronchiectasis and Its Association With Clinical Findings.

OBJECTIVE: This study was designed to assess obstructive sleep apnea (OSA) in adult patients with cystic fibrosis (CF) and non-CF bronchiectasis (BE) and to relate it with clinical characteristics. METHODS: Thirty-five CF (27 years) and 35 non-CF (24 years) BE patients were included. Demographic characteristics, medications, comorbidities, BMI, dyspnea scales, pulmonary functions, sputum cultures, exacerbations, and hospitalizations were recorded. The Epworth Sleepiness Scale (ESS) questionnaire was filled and polysomnography was performed for each patient. RESULTS: ESS scores did not show any significant difference between CF and non-CF BE patients. Thirty-seven (53%) of all patients had OSA. There was no significant difference in OSA risk between CF and non-CF BE patients (54% vs 51%, respectively). Male gender was found to be a risk factor for OSA (68% of males vs 41% of females, respectively, p:0.026). Total sleep time, sleep efficiency, sleep latency, time spent awake after falling asleep, oxygen desaturation index, apnea-hypopnea-index (AHI), AHI in the supine position, and rapid eye movement phase did not show any significant difference between CF and non-CF patients. CF patients had significantly lower mean oxygen saturation (p:0.001) and lowest oxygen saturation (p:0.0024) levels and higher heart rate (p:0.02) compared to non-CF BE patients. Multiple logistic regression analysis of all patients revealed male gender and disease duration as risk factors for OSA (p:0.023 and p:0.041 respectively). CONCLUSION: It is remarkable that more than half of the patients in both CF and non-CF bronchiectasis groups had OSA. Male gender and disease duration were found as risk factors for OSA.

REM-Predominant Obstructive Sleep Apnea in Patients with Coronary Artery Disease.

Obstructive sleep apnea (OSA) is common in adults with coronary artery disease (CAD). OSA that occurs predominantly during rapid-eye movement (REM) sleep has been identified as a specific phenotype (REM-predominant OSA) in sleep clinic cohorts. We aimed to examine the association of REM-predominant OSA with excessive sleepiness, functional outcomes, mood, and quality of life in a CAD cohort, of whom 286 OSA patients with total sleep time ≥ 240 min, and REM sleep ≥ 30 min, were included. REM-predominant OSA was defined as a REM-apnea-hypopnea-index (AHI) /non-REM (NREM) AHI ≥ 2. In all, 73 (25.5%) had REM-predominant OSA. They were more likely to be female (26.0% vs. 9.9%; p = 0.001), and more obese (42.5% vs. 24.4%; p = 0.003) but had less severe OSA in terms of AHI (median 22.6/h vs. 36.6/h; p < 0.001) compared to the patients with non-stage specific OSA. In adjusted logistic regression models, female sex (odds ratio [OR] 4.64, 95% confidence interval [CI] 1.85−11.64), body-mass-index (BMI; OR 1.17; 95% CI 1.07−1.28) and AHI (OR 0.93, 95% CI 0.91−0.95) were associated with REM-predominant OSA. In univariate linear regression models, there was a dose-response relationship between REM-AHI and Zung Self-rated Depression Scale but not excessive sleepiness, functional outcomes, and anxiety scores. Among the Short Form-36 subdomains, Vitality, Mental Health, and Mental Component Summary (MCS) scores were inversely correlated with REM-AHI. In multivariate linear models, only MCS remained significantly associated with REM-AHI after adjustment for age, BMI, and sex (ß-coefficient −2.20, %95 CI [−0.56, −0.03]; p = 0.028). To conclude, female sex and BMI were related to REM-predominant OSA in this revascularized cohort. MCS was inversely associated with REM-AHI in the multivariate model.

CPAP Intervention as an Add-On Treatment to Lipid-Lowering Medication in Coronary Artery Disease Patients with Obstructive Sleep Apnea in the RICCADSA Trial.

Dyslipidaemia is a well-known risk factor for coronary artery disease (CAD), and reducing lipid levels is essential for secondary prevention in management of these high-risk individuals. Dyslipidaemia is common also in patients with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) is the first line treatment of OSA. However, evidence of a possible lipid-lowering effect of CPAP in CAD patients with OSA is scarce. We addressed the effect of CPAP as an add-on treatment to lipid-lowering medication in a CAD cohort with concomitant OSA. This study was a secondary analysis of the RICCADSA trial (Trial Registry: ClinicalTrials.gov; No: NCT00519597), that was conducted in Sweden between 2005 and 2013. In total, 244 revascularized CAD patients with nonsleepy OSA (apnea-hypopnea index ≥ 15/h, Epworth Sleepiness Scale score < 10) were randomly assigned to CPAP or no-CPAP. Circulating triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels (all in mg/dL) were measured at baseline and 12 months after randomization. The desired TG levels were defined as circulating TG < 150 mg/dL, and LDL levels were targeted as <70 mg/dL according to the recent guidelines of the European Cardiology Society and the European Atherosclerosis Society. A total of 196 patients with available blood samples at baseline and 12-month follow-up were included (94 randomized to CPAP, 102 to no-CPAP). We found no significant between-group differences in circulating levels of TG, TC, HDL and LDL at baseline and after 12 months as well as in the amount of change from baseline. However, there was a significant decline regarding the proportion of patients with the desired TG levels from 87.2% to 77.2% in the CPAP group (p = 0.022), whereas there was an increase from 84.3% to 88.2% in the no-CPAP group (n.s.). The desired LDL levels remained low after 12 months in both groups (15.1% vs. 17.2% in CPAP group, and 20.8% vs. 18.8% in no-CPAP group; n.s.). In a multiple linear regression model, the increase in the TG levels was predicted by the increase in body-mass-index (ß = 4.1; 95% confidence interval (1.0-7.1); p = 0.009) adjusted for age, sex and CPAP usage (hours/night). CPAP had no lipid-lowering effect in this revascularized cohort with OSA. An increase in body-mass-index predicted the increase in TG levels after 12 months, suggesting that lifestyle modifications should be given priority in adults with CAD and OSA, regardless of CPAP treatment.

Association of Excessive Daytime Sleepiness with the Zung Self-Rated Depression Subscales in Adults with Coronary Artery Disease and Obstructive Sleep Apnea.

Excessive daytime sleepiness (EDS) is a factor associated with both obstructive sleep apnea (OSA) and depressive symptoms. Continuous positive airway pressure (CPAP) treatment may decrease EDS in adults with OSA; however, the modulatory role of depressive symptoms on the improvement of EDS is not known. We aimed to explore the association between subscales of the Zung Self-rated Depression Scale (SDS) and Epworth Sleepiness Scale (ESS) over a 2-year period in coronary artery disease (CAD) patients with OSA. This was a post-hoc analysis of the RICCADSA cohort, in which 399 adults with CAD (155 sleepy OSA [apnea-hypopnea index ≥ 15/h] and ESS score ≥ 10, who were offered CPAP; and 244 nonsleepy OSA [ESS < 10]), randomized to CPAP [n = 122] or no-CPAP [n = 122]) were included. Three factors were extracted from the Zung SDS, based on the principal component analysis: F1, cognitive symptoms and anhedonia; F2, negative mood; and F3, appetite. In a mixed model, the ESS score decreased by 3.4 points (p < 0.001) among the sleepy OSA phenotype, which was predicted by the decline in the F2, but not in the F1 and F3 scores. The fixed effects of time were not significant in the nonsleepy OSA groups, and thus, further analyses were not applicable. Additional within-group analyses showed a significant decrease in all subscales over time both in the sleepy and nonsleepy OSA patients on CPAP whereas there was a significant increase in the nonsleepy OSA group randomized to no-CPAP. We conclude that the improvement in negative mood symptoms of depression, but not changes in cognitive symptoms and anhedonia as well as appetite, was a significant predictor of decline in the ESS scores over a 2-year period in this CAD cohort with sleepy OSA on CPAP treatment.

Impact of Gender on Symptoms and Comorbidities in Obstructive Sleep Apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is more common in men than in women. In this study, we aimed to address the impact of gender on symptoms and comorbidities in patients with OSA. MATERIALS AND METHODS: This cross-sectional study was conducted among 1,317 consecutive patients, who were admitted to the Sleep Apnea Clinic of the Marmara University Hospital between November 2015 and October 2018, and who completed questionnaires and a sleep study with cardiorespiratory polygraphy. OSA was defined as Apnea Hypopnea Index (AHI) ≥15/hour. RESULTS: In all, 1,042 patients (334 women) fulfilled the inclusion criteria. OSA was observed in 589 patients (56.5%). Women were older than men (50.2±12.5 versus 45.6±15.1 years) and had lower AHI (22.1±20.1 versus 26.8±21.9 events/h). In the OSA group, women were older (53.7±11.5 versus 47.8±12.8 years) and more obese (BMI 34.6 versus 31.8 kg/m2). Symptoms were categorized as frequent/very frequent, and women with OSA complained more about daytime fatigue (74.6% versus 63.7%), nocturia (69.7% versus 51.8%), headache in the morning (50.0% versus 28.4%), depressive mood (49.0% versus 19.5%), and restless legs symptoms (43.1% versus 17.2%), than did men (all p values <0.05). Comorbidities were observed more in women than in men (lung disease [25.4% versus 13.7%], hypertension [29.6% versus 15.0%], diabetes [20.3% versus 11.3%], and hypothyroidism [14.0 % versus 4.1%]). In regression analysis, age (OR 1.03, p<0.001), BMI (OR 1.13, p<0.001), and male sex (OR 2.08, p<0.001) were significantly predictive for OSA while history of tonsillectomy was protective (OR 0.48, p=0.033). CONCLUSION: Fatigue, nocturia, headache, depressive mood, restless leg, and comorbidities were observed more in women. OSA-related symptoms develop late and/or the referral of women for diagnostic evaluation of OSA is delayed. Symptoms and comorbidities in women should be evaluated more attentively for earlier referral and diagnosis of OSA.

Effect of High-Risk Obstructive Sleep Apnea on Clinical Outcomes in Adults with Coronavirus Disease 2019: A Multicenter, Prospective, Observational Clinical Trial.

Rationale: Coronavirus disease (COVID-19) is an ongoing pandemic, in which obesity, hypertension, and diabetes have been linked to poor outcomes. Obstructive sleep apnea (OSA) is associated with these conditions and may influence the prognosis of adults with COVID-19. Objectives: To determine the effect of OSA on clinical outcomes in patients with COVID-19. Methods: The current prospective observational study was conducted in three hospitals in Istanbul, Turkey from March 10 to June 22, 2020. The participants were categorized as high-risk or low-risk OSA according to the Berlin questionnaire that was administered in the out-patient clinic, in hospital, or shortly after discharge from hospital blinded to the clinical outcomes. A modified high-risk (mHR)-OSA score based on the snoring patterns (intensity and/or frequency), breathing pauses, and morning/daytime sleepiness, without taking obesity and hypertension into account, were used in the regression models. Results: The primary outcome was the clinical improvement defined as a decline of two categories from admission on a 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death) on Days 7, 14, 21, and 28, respectively. Secondary outcomes included clinical worsening (an increase of 1 category), need for hospitalization, supplemental oxygen, and intensive care. In total, 320 eligible patients (median [interquartile range] age, 53.2 [41.3-63.0] yr; 45.9% female) were enrolled. In all, 121 (37.8%) were categorized as known (n = 3) or high-risk OSA (n = 118). According to the modified scoring, 70 (21.9%) had mHR-OSA. Among 242 patients requiring hospitalization, clinical improvement within 2 weeks occurred in 75.4% of the mHR-OSA group compared with 88.4% of the modified low-risk-OSA group (P = 0.014). In multivariate regression analyses, mHR-OSA (adjusted odds ratio [OR], 0.42; 95% confidence interval [CI], 0.19-0.92) and male sex (OR, 0.39; 95% CI, 0.17-0.86) predicted the delayed clinical improvement. In the entire study population (n = 320), including the nonhospitalized patients, mHR-OSA was associated with clinical worsening (adjusted hazard ratio, 1.55; 95% CI, 1.00-2.39) and with the need for supplemental oxygen (OR, 1.95; 95% CI, 1.06-3.59). Snoring patterns, especially louder snoring, significantly predicted delayed clinical improvement, worsening, need for hospitalization, supplemental oxygen, and intensive care. Conclusions: Adults with mHR-OSA in our COVID-19 cohort had poorer clinical outcomes than those with modified low-risk OSA independent of age, sex, and comorbidities. Clinical trial registered with www.clinicaltrials.gov (NCT04363333).

Impact of concomitant obstructive sleep apnea on pulmonary involvement and main pulmonary artery diameter in adults with scleroderma.

PURPOSE: Pulmonary involvement is common in adults with scleroderma. The effect of concomitant obstructive sleep apnea (OSA) on risk for pulmonary hypertension in scleroderma is unknown. An enlarged main pulmonary artery diameter (mPAD) derived from chest computer tomography (CT) is a useful predictor of pulmonary hypertension. We addressed the effect of OSA on pulmonary involvement and enlarged mPAD in adults with scleroderma. METHODS: All participants underwent pulmonary function testing, carbon monoxide diffusion capacity, chest CT, and overnight sleep recording with home sleep apnea testing. OSA diagnosis was based on an apnea-hypopnea index (AHI) ≥ 15/h. Oxygen desaturation index (ODI) was also recorded. Scleroderma involvement of the lungs was defined as the Warrick score ≥ 7 based on the CT findings. Enlarged mPAD was defined as an mPAD ≥ 29 mm in men and ≥ 27 mm in women. RESULTS: After exclusions, 62 patients (58 women) were included. OSA was found among 20 (32%), 17/42 (38%) in the limited cutaneous type, and 3/20 (15%) in the diffuse cutaneous type (p = 0.08). Scleroderma involvement of the lungs was observed in 40 participants (65% in OSA vs 64% in no-OSA; n.s.). Enlarged mPAD was measured in 16 participants, 10 of 20 (50%) in the OSA group and 6 of 17 (14%) in the no-OSA group (p = 0.003). OSA was associated with enlarged mPAD (odds ratio 4.7, 95% confidence interval 1.1-20.9; p = 0.042) independent of age, body mass index, and pulmonary involvement. There was a linear relationship between mPAD and AHI (r = 0.37; p = 0.003) as well as ODI (r = 0.41; p < 0.001). CONCLUSIONS: In this cohort, OSA was associated with risk for pulmonary hypertension independent of pulmonary involvement. These findings suggest that assessing the effect of therapy for concomitant OSA in patients with scleroderma is warranted. TRIAL REGISTRATION: NCT02740569.

Clinical impact of depression and anxiety in patients with non-cystic fibrosis bronchiectasis.

INTRODUCTION: Bronchiectasis is a chronic suppurative disease characterized by abnormal bronchial dilatation. The nature of bronchiectasis may have negative impact on psychological status, however it is poorly studied in relation to clinical indices, particularly the severity of disease. Primary aim of this study is to detect depression and anxiety in patients with non-cystic fibrosis bronchiectasis and to evaluate its relationship with disease severity indexes. MATERIALS AND METHODS: Ninety (male/female= 37/53; median age 45 years) stable non-cystic fibrosis bronchiectatic adult patients were enrolled into this study. Dyspnea scores, number of exacerbations and hospital admissions within the last year, body-mass index, pulmonary function tests, sputum cultures, bronchiectasis disease severity indexes (BSI and FACED) were assessed. Anxiety and depression were evaluated by using the Turkish version of the hospital anxiety and depression scale questionaire. RESULT: Anxiety was diagnosed in 30% of patients and depression was diagnosed in 41% of the participants. Female participants had significantly higher rates of depression (55% vs. 22%; p= 0.002). Exacerbation rates within the last year were higher among the subjects with anxiety, moreover, patients with depression had shorter duration of disease. BSI and FACED severity indexes increased with longer duration of disease (5.6 ± 5.0 yrs in mild group vs. 10.1 ± 9.2 yrs in moderate-to-severe group, p= 0.035 and 5.7 ± 5.4 yrs in mild group vs. 12.1 ± 9.7 yrs in moderate-to-severe group, p= 0.001, respectively), however, anxiety and depression were not related with BSI and FACED severity indexes. CONCLUSIONS: Patients with non-cystic fibrosis bronchiectasis have an increased risk for depression and anxiety. Duration of disease and higher exacerbation rate are related with psychological status and indexes increased with longer duration of disease. Early detection and taking the necessary measures to improve the psychological state is necessary for the overall management of these patients.

Impact of CPAP treatment on leptin and adiponectin in adults with coronary artery disease and nonsleepy obstructive sleep apnoea in the RICCADSA trial.

BACKGROUND: Increased leptin and decreased adiponectin levels are reported in coronary artery disease (CAD) as well as in obstructive sleep apnoea (OSA). Less is known regarding the impact of continuous positive airway pressure (CPAP) on these biomarkers. We aimed to determine variables associated with leptin and adiponectin in adults with CAD and nonsleepy OSA, and evaluate the effect of CPAP adjusted for confounding factors. METHODS: This was one of the secondary outcomes of the RICCADSA trial, conducted in Sweden between 2005 and 2013. From 244 revascularized CAD and OSA patients (apnoea-hypopnoea index >15/h) without excessive daytime sleepiness (Epworth Sleepiness Scale score <10), 196 with blood samples at baseline, after 3, and 12 months were included in the randomized controlled trial arm; of those, 98 were allocated to auto-titrating CPAP, and 98 to no-CPAP. RESULTS: No significant changes in leptin and adiponectin levels were observed during follow-up, whereas Body-Mass-Index and waist circumference increased in both CPAP and no-CPAP groups with no significant between-group differences. Alterations in plasma leptin were determined by changes in waist circumference (beta coefficient 2.47; 95% confidence interval 0.77-4.40), whereas none of the analyzed parameters was predictive for changes in adiponectin levels. No association was found with CPAP adherence. CONCLUSIONS: CPAP had no significant effect on leptin and adiponectin in this cohort of nonsleepy OSA patients. An increase in waist circumference predicted an increase in plasma levels of leptin after 12 months, suggesting that lifestyle modifications should be given priority in adults with CAD and OSA regardless of CPAP treatment.

CPAP and Health-Related Quality of Life in Adults With Coronary Artery Disease and Nonsleepy Obstructive Sleep Apnea in the RICCADSA Trial.

STUDY OBJECTIVES: To determine the effect of continuous positive airway pressure (CPAP) treatment on health-related quality of life (HRQoL) in adults with coronary artery disease (CAD) and nonsleepy obstructive sleep apnea (OSA). METHODS: This was a secondary outcome analysis of the RICCADSA trial, conducted in Sweden between 2005 and 2013. Adults with CAD, nonsleepy OSA (apnea-hypopnea index [AHI] ≥ 15 events/h; Epworth Sleepiness Scale [ESS] score < 10) and complete Short-Form (SF)-36 questionnaires at baseline and after 12 months were included. Patients were randomized to CPAP (n = 102) or no CPAP (n = 104). The primary outcome was the between-group difference in absolute change in the SF-36 components. Within-group changes as well as variables associated with absolute change in the domains in the entire population were also tested. RESULTS: Mean SF-36 scores were similar at baseline, ranging from 44.9 ± 9.6 to 92.2 ± 15.8 in various domains, and between-group changes from baseline were not statistically significant at 1 year. There was a significant increase in Role physical, Vitality, Role emotional, Mental health and Mental Component Summary (MCS), and a decrease in Bodily pain and General health scores in the CPAP group. The change in Physical Component Summary (PCS) was determined by female sex (beta coefficient -0.19, 95% confidence interval [CI] -7.25 to -0.98, P = .010), baseline AHI (beta coefficient -0.19, 95% CI -0.21 to -0.03, P = .009), CPAP use (h/night) (beta coefficient -0.16, 95% CI -0.93 to -0.06, P = .028), and acute myocardial infarction at baseline (beta coefficient 0.18, 95% CI 0.59 to 5.19, P = .014). Determinants of the change in MCS from baseline were change in the ESS score (beta coefficient -0.14, 95% CI -0.87 to -0.01, P = .054) and change in the Zung Self-rated Depression Scale scores (beta coefficient -0.33, 95% CI -0.58 to -0.24, P < .001). CONCLUSIONS: Assignment to CPAP treatment compared to no CPAP had no significant effect on HRQoL as measured by the SF-36 in adults with CAD and nonsleepy OSA. Although several components of the SF-36 scores were improved within the CPAP group, CPAP use was associated with a decrease in PCS. The improvement in MCS was determined by the improvement in daytime sleepiness and depressive mood. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Identifier: NCT00519597. CITATION: Wallström S, Balcan B, Thunström E, Wolf A, Peker Y. CPAP and health-related quality of life in adults with coronary artery disease and nonsleepy obstructive sleep apnea in the RICCADSA trial. J Clin Sleep Med. 2019;15(9):1311-1320.

Determinants of depressive mood in coronary artery disease patients with obstructive sleep apnea and response to continuous positive airway pressure treatment in non-sleepy and sleepy phenotypes in the RICCADSA cohort.

We explored determinants of depressive mood in adults with coronary artery disease and obstructive sleep apnea and response to positive airway pressure treatment in sleepy and non-sleepy phenotypes. In this secondary analysis of the RICCADSA trial conducted in Sweden, 493 cardiac patients with obstructive sleep apnea (n = 386) or no obstructive sleep apnea (n = 107) with complete Epworth Sleepiness Scale and Zung Self-rating Depression Scale questionnaires were included. Sleepy (Epworth Sleepiness Scale ≥10) versus non-sleepy (Epworth Sleepiness Scale <10) patients with depressive mood (Zung Self-rating Depression Scale score ≥50) were evaluated after 3 and 12 months of positive airway pressure treatment. In all, 133 patients (27.0%) had depressive mood (29.3% of obstructive sleep apnea versus 18.7% of no obstructive sleep apnea; p = 0.029), with a higher percentage among the sleepy phenotype (36.9% versus 24.5%; p = 0.009). In multivariate analysis, depressive mood was significantly associated with female sex, body mass index and Epworth Sleepiness Scale. Among 97 obstructive sleep apnea patients with depressive mood at baseline, there was a significant reduction in the scores at follow-up both in the sleepy and non-sleepy patients allocated to positive airway pressure treatment, whereas no significant changes were observed in the untreated group (p = 0.033). The device use (hr/night) predicted improvement in mood (odds ratio, 1.33; 95% confidence interval, 1.10-1.61; p = 0.003) adjusted for age, female sex, body mass index, left ventricular ejection fraction, apnea-hypopnea index and delta Epworth Sleepiness Scale score. We conclude that obstructive sleep apnea was associated with depressive mood in adults with coronary artery disease. Treatment with positive airway pressure improved mood in both phenotypes, independent of the confounding factors.

Continuous Positive Airway Pressure Treatment and Depression in Adults with Coronary Artery Disease and Nonsleepy Obstructive Sleep Apnea. A Secondary Analysis of the RICCADSA Trial.

RATIONALE: Obstructive sleep apnea (OSA) and depression are common among adults with coronary artery disease (CAD). OBJECTIVES: To determine the impact of continuous positive airway pressure (CPAP) treatment on depression in adults with CAD and nonsleepy OSA. METHODS: This was a secondary analysis of the RICCADSA (Randomized Intervention with CPAP in CAD and Sleep Apnea) trial, conducted in Sweden between 2005 and 2013. Adults with CAD and nonsleepy OSA (apnea-hypopnea index ≥15/h, and Epworth Sleepiness Scale <10 at baseline) and complete Zung Self-Rating Depression Scale (SDS) questionnaires at baseline, after 3 and 12 months, were included. Participants analyzed in their randomized arm were CPAP (n = 99) or no-CPAP (n = 104). Depression was defined as a Zung SDS score of 50 or greater. The primary outcome was the between-group difference in the absolute change in the SDS score from baseline. RESULTS: No significant between-group differences were observed in SDS scores during follow-up in the entire study sample. Among the 56 participants with an SDS of 50 or greater at baseline (27.6%), the mean (±SD) baseline SDS was 55.0 (±5.5) in the CPAP group, and 53.9 (±4.0) in the no-CPAP group. In the CPAP group, SDS scores decreased at 3 months (47.2 ± 8.2) and 12 months (45.8 ± 7.6), but remained stable in the no-CPAP group at 3 months (53.1 ± 8.0) and 12 months (52.6 ± 8.1) (P = 0.01). The proportion with depression decreased from 30.3% at baseline to 16.2% after 3 months, and to 13.1% after 12 months in the CPAP group, from 25.0% at baseline to 23.1% after 3 months, and to 24.0% after 12 months in the no-CPAP group (P = 0.001). Moreover, there was an association between the duration of CPAP usage (h/night) and the longitudinal decline in SDS score (r = 0.46; P < 0.001). CPAP usage categories (3, 4, and 5 h/night) were significantly associated with improvement in SDS (odds ratio = 3.92, 4.45, and 4.89, respectively) in multivariate analyses adjusted for age, sex, body mass index, left ventricular ejection fraction, apnea-hypopnea index, and Epworth Sleepiness Scale at baseline. CONCLUSIONS: Among adults with depression, nonsleepy OSA, and CAD, 3 months of CPAP treatment improved depression scores. The improvement in mood persisted up to 12 months. An on-treatment adjusted analysis confirmed these findings. Clinical trial registered with www.clinicaltrials.gov (NCT00519597).

Altered pulmonary functions due to biomass smoke in a rural population of Turkish women: a descriptive study.

INTRODUCTION: Wood or other organic sources of fuel are used as source of energy for heating or cooking particularly in developing countries. The aim of the current study was to evaluate the association between biomass exposure time and parameters of pulmonary function tests. MATERIALS AND METHODS: Four hundred twenty-four consecutive women who lived and exposed to biomass smoke in a small province in Eastern Turkey were involved. This study was performed with women who had come to pulmonology out-patient clinic with symptom of dyspnea. RESULT: The independent variables assessed in the study patients were age, BMI, starting age of cooking, hours per day and weeks per month spent cooking, and cooking years; the dependent variables were PFT parameters. Ninety-two (21.6%) patients had an obstructive PFT pattern. Sixty-seven (73%) of these patients were classified as GOLD 2 and 25 (27%) patients were classified as GOLD 3. Seventy-five (17.6 %) of the patients had restrictive lung disease; 54 (72%) of these patients were found to have a mild and 21 (27%) had a moderate restrictive pattern. Increased number of years in cooking and to start cooking at younger ages were a risk factors for the development of obstructive and restrictive disease. There was a statistically significant and negative correlation between increased number of years and the value of FEV1 (r= -0.917; p=< 0.001), FEV1/FVC (r= -0.739; p< 0.001), and FVC (r= -0.906; p< 0.001). The median time of cooking required was 23 years for the development of obstruction, and 25 years for restriction, respectively. CONCLUSIONS: Cumulative biomass exposure time is associated with impairment in PFT parameters; results in both obstructive and restrictive lung disease. Biomass exposure is a public health problem and pre-cautions should be taken in order to prevent impaired pulmonary functions.

Increased Mortality Among Renal Transplant Patients With Invasive Pulmonary Aspergillus Infection.

INTRODUCTION: Renal transplantation is the most effective and preferred definite treatment option in patients with end-stage renal disease. Due to long-term immunesuppressive treatment, renal transplant recipients become vulnerable to opportunistic infections, especially to fungal infections. METHOD: This was a single-center, retrospective observational study of 438 patients who underwent renal transplantation between 2010 and 2016. RESULTS: Thirty-eight renal transplant recipients who had lower respiratory tract infection with median age of 41.5 years were evaluated for invasive pulmonary aspergillus (IPA). Of these, 52.6% were female and 84.2% had living donors. Eleven of 38 lower respiratory patients were found to have IPA infection, 5 with proven infection. Compared to patients who did not have fungal pulmonary infection, patients with invasive aspergillus were older and had high fever, galactomannan levels, and leukocyte counts. Mortality was also higher in those patients. Having fever at the baseline and IPA infection was significantly associated with mortality in univariate analysis and remained related in multivariate model after adjustment for age, gender, and fever. CONCLUSION: Invasive pulmonary aspergillus infection is highly associated with increased mortality rates in renal transplant patients. Fungal pulmonary infections in immune-suppressed patients should be diagnosed and treated immediately in order to avoid the life-threatening complications and may greatly improve prognosis.

Cardiovascular outcomes of continuous positive airway pressure therapy for obstructive sleep apnea.

Obstructive sleep apnea is a common disorder with increased risk for cardiovascular morbidity and mortality. The first choice of treatment of obstructive sleep apnea is continuous positive airway pressure, which reduces excessive daytime sleepiness and improves quality of life in sleep clinic cohorts. Nevertheless, the majority of patients with cardiovascular disease and concomitant obstructive sleep apnea do not report daytime sleepiness, and adherence to treatment is insufficient particularly in this group. The current article aims to give an updated overview of the impact of continuous positive airway pressure therapy on cardiovascular outcomes mainly based on the observational studies and the recent randomized controlled trials.